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01.08.2011 | Original article

Dendritic cell-based vaccination of patients with advanced pancreatic carcinoma: results of a pilot study

verfasst von: Christian Bauer, Marc Dauer, Samira Saraj, Maximilian Schnurr, Franz Bauernfeind, Alexander Sterzik, Jana Junkmann, Veronika Jakl, Rosemarie Kiefl, Fuat Oduncu, Bertold Emmerich, Doris Mayr, Thomas Mussack, Christiane Bruns, Dominik Rüttinger, Claudius Conrad, Karl-Walter Jauch, Stefan Endres, Andreas Eigler

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 8/2011

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Abstract

Background and aims

Dendritic cell (DC)-based vaccination can induce antitumor T cell responses in vivo. This clinical pilot study examined feasibility and outcome of DC-based tumor vaccination for patients with advanced pancreatic adenocarcinoma.

Methods

Tumor lysate of patients with pancreatic carcinoma was generated by repeated freeze–thaw cycles of surgically obtained tissue specimens. Patients were eligible for DC vaccination after recurrence of pancreatic carcinoma or in a primarily palliative situation. DC were generated from peripheral blood mononuclear cells (PBMC), loaded with autologous tumor lysate, stimulated with TNF-α and PGE₂ and injected intradermally. All patients received concomitant chemotherapy with gemcitabine. Disease response was the primary endpoint. Individual immunological responses to DC vaccination were analyzed by T cell-based immunoassays using pre- and post-vaccination samples of non-adherent PBMC.

Results

Twelve patients received DC vaccination and concomitant chemotherapy. One patient developed a partial remission, and two patients remained in stable disease. Median survival was 10.5 months. No severe side effects were observed. Tumor-reactive T cells could be detected prior to vaccination. DC vaccination increased the frequency of tumor-reactive cells in all patients tested; however, the degree of this increase varied. To quantify the presence of tumor-reactive T cells, stimulatory indices (SI) were calculated as the ratio of proliferation-inducing capacity of lysate-loaded versus -unloaded DC. The patient with longest overall survival of 56 months had a high SI of 6.49, indicating that the presence of a pre-vaccination antitumor T cell response might be associated with prolonged survival. Five patients survived 1 year or more.

Conclusion

DC-based vaccination can stimulate an antitumoral T cell response in patients with advanced or recurrent pancreatic carcinoma receiving concomitant gemcitabine treatment.

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Titel: Dendritic cell-based vaccination of patients with advanced pancreatic carcinoma: results of a pilot study
verfasst von: Christian Bauer
Marc Dauer
Samira Saraj
Maximilian Schnurr
Franz Bauernfeind
Alexander Sterzik
Jana Junkmann
Veronika Jakl
Rosemarie Kiefl
Fuat Oduncu
Bertold Emmerich
Doris Mayr
Thomas Mussack
Christiane Bruns
Dominik Rüttinger
Claudius Conrad
Karl-Walter Jauch
Stefan Endres
Andreas Eigler
Publikationsdatum: 01.08.2011
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 8/2011
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1023-5

Springer Medizin

Dendritic cell-based vaccination of patients with advanced pancreatic carcinoma: results of a pilot study